Interactions Determining Stereoselectivity in Two-Dimensional Systems─The Case of 22-Hydroxycholesterol Epimers

Area of Science:

• Biochemistry and Biophysics
• Membrane Biology
• Physical Chemistry

Background:

• Oxidized cholesterol derivatives (oxysterols) are vital for biomembrane function.
• Unlike many biomolecules, some oxysterols exist as stereoisomers with differing biological effects.
• 22-hydroxycholesterol (22-OH) epimers, 22(R)-OH and 22(S)-OH, represent such stereoisomers.

Purpose of the Study:

• To investigate the distinct properties of 22(R)-OH and 22(S)-OH epimers.
• To examine their behavior in Langmuir monolayers at the air/water interface.
• To understand how stereochemistry influences oxysterol interactions with sphingomyelin (SM).

Main Methods:

• Langmuir monolayers formed at the air/water interface.
• Surface manometry for isotherm measurements.
• Brewster angle microscopy (BAM) for film texture analysis.
• Molecular dynamics (MD) simulations for structural and interaction insights.

Main Results:

• 22(S)-OH formed condensed, homogeneous monolayers with high collapse pressure.
• 22(R)-OH formed expanded, disordered monolayers with low collapse pressure, exhibiting temperature-dependent domain coexistence.
• Both epimers interacted similarly with sphingomyelin, but film composition differed due to stereochemistry-driven hydrogen bonding.

Conclusions:

• Oxysterol stereochemistry critically influences their physical properties and membrane organization.
• The greater hydration of 22(R)-OH contributes to its structural variability.
• Stereospecific hydrogen bonding governs the differential interactions of 22-OH epimers with membrane lipids like SM.